Control of enantioselectivity in the enzymatic reduction of halogenated acetophenone analogs by substituent positions and sizes. Issue 18 (30th April 2020)

• Record Type: Journal Article
• Authors: Koesoema, Afifa Ayu; Standley, Daron M.; Ohshima, Shusuke; Tamura, Mayumi; Matsuda, Tomoko
• Is Part Of: Tetrahedron letters. Volume 61:Issue 18(2020)
• Publication Date: 2020-04-30
• Subjects: Enantioselectivity control -- Alcohol dehydrogenase -- Asymmetric reduction -- Halogenated acetophenone analogs; Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1016/j.tetlet.2020.151820
• Languages: English
• ISSNs: 0040-4039

Abstract

Graphical abstract: Highlights: An alcohol dehydrogenase was used to reduce halogenated acetophenone analogs. ( S )- and ( R )-alcohols of beneficial pharmaceutical intermediates were synthesized. ( S )-Alcohols with >99% ee were obtained using the wild type. The selectivity of Trp288Ala was controlled by substituents positions and sizes. ( R )-Alcohols with up to 99% ee were obtained using Trp288Ala. Abstract: We utilized acetophenone reductase from Geotrichum candidum NBRC 4597 ( Gc APRD), wild type and Trp288Ala mutant, to reduce halogenated acetophenone analogs to their corresponding ( S )- and ( R )-alcohols beneficial as pharmaceutical intermediates. Reduction by wild type resulted in excellent ( S )-enantioselectivity for all of the substrates tested. Meanwhile, reduction by Trp288Ala resulted in high ( R )-enantioselectivity for the reduction of 4′ substituted acetophenone and 2′-trifluoromethylacetophenone. In addition to that, we were able to control the enantioselectivity of Trp288Ala by the positions and sizes of the halogen substituents.